Escitalopram for Anxiety

(PrEcISE Trial)

Overseen By Heidi K Schroeder, BS

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Cincinnati

Must not be taking: SSRIs, Psychiatric medications

Disqualifiers: Mood disorders, Intellectual disability, Trauma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

132 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods of using the medication escitalopram (also known as Lexapro or Cipralex) to treat anxiety disorders in teens. One group will receive a standard dose, while the other will have their dose adjusted based on their body's ability to process the drug. Teens aged 12-17 with generalized, social, or separation anxiety who have not recently started new therapy might be suitable candidates. The goal is to determine which dosing method more effectively reduces anxiety symptoms. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to understand how it can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that participants have not been treated with SSRIs (a type of antidepressant) within 12 weeks of starting the study and not be on any medication with psychiatric effects that need more than 5 half-lives to clear from the body. If you're on such medications, you may need to stop them before joining the trial.

What is the safety track record for escitalopram?

Research has shown that escitalopram is generally safe for treating anxiety. In past studies, the FDA approved escitalopram for adults and children aged 7 and older with generalized anxiety disorder, indicating a strong safety record.

The side effects are well-known and usually mild, with serious issues being rare. The FDA advises adults not to exceed 20 mg per day to prevent possible heart-related problems.

Overall, escitalopram is considered safe for treating anxiety, especially when taken at the recommended doses. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the trial for escitalopram dosing for anxiety because it explores a personalized approach to treatment. Unlike standard dosing, which typically starts at a fixed low dose and gradually increases, this trial uses pharmacogenetics to tailor doses based on a patient's CYP2C19 genetic makeup. This means that poor metabolizers can receive a dose more suited to their body's ability to process the medication, potentially leading to better outcomes and fewer side effects. This personalized dosing strategy could revolutionize how we approach anxiety treatment, making it more effective and patient-specific.

What is the effectiveness track record for escitalopram in treating anxiety?

Research has shown that escitalopram effectively treats anxiety disorders. One study found escitalopram significantly more effective than a placebo for social anxiety. Another study demonstrated its superiority over citalopram, a similar medication, in quickly improving depression symptoms related to anxiety. Escitalopram is commonly used for anxiety-related conditions, including social anxiety and panic disorders. Experts agree that escitalopram is an effective treatment for anxiety.

In this trial, participants will be randomized into two treatment arms: one receiving standard dosing of escitalopram and the other receiving pharmacogenetically-guided escitalopram dosing. ^{1 6 7 8 9}

Who Is on the Research Team?

Jeffrey R Strawn, MD, FAACAP

Principal Investigator

University of Cincinnati

Laura B Ramsey, PhD

Principal Investigator

Children's Mercy Kansas City

Are You a Good Fit for This Trial?

This trial is for youths aged 12-17 with generalized, social, or separation anxiety disorder. They must have a certain severity of anxiety, no recent psychotherapy initiation, and be English-speaking. Participants need normal physical exams and EKGs, not be pregnant or drug-positive, and use reliable contraception if sexually active.

Inclusion Criteria

I am between 12 and 17 years old.

Your overall level of symptoms is rated as moderate to severe by the doctor during two visits.

Caregiver who is willing to consent to be responsible for safety monitoring of the patient, provide information about the patient's condition, oversee the administration of the investigational product

Exclusion Criteria

You have a mood disorder like depression, eating disorder, bipolar disorder, or psychotic disorder, except for specific types of depression and anxiety disorders.

A positive urine drug screen

You have experienced allergies, intolerance, non-response, or extreme sensitivity to escitalopram.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard or pharmacogenetically-guided escitalopram dosing for 12 weeks

12 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Escitalopram

Trial Overview The study tests escitalopram dosing in anxious youth over 12 weeks. It's double-blind with participants randomly assigned to standard dosing or doses guided by their genetics. The randomization considers sex and how well their body processes drugs.

How Is the Trial Designed?

Group I: Standard dosing Experimental Treatment 1 Intervention

Patients randomized to standard dosing (std) will initiate escitalopram at 5 mg daily and will then increase to 20 mg/day at week 4.

Group II: Pharmacogenetically-guided escitalopram dosing Experimental Treatment 1 Intervention

Patients randomized to PGx-guided treatment, escitalopram titration will be based on CYP2C19 phenotype and predicted escitalopram exposure. In poor metabolizers (PM), escitalopram will be initiated at 5 mg daily and increased to 10 mg daily at week 4.

Escitalopram is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Lexapro for:

• Major depressive disorder
• Generalized anxiety disorder

Approved in European Union as Cipralex for:

• Major depressive episodes
• Generalized anxiety disorder
• Social anxiety disorder
• Panic disorder with or without agoraphobia
• Obsessive-compulsive disorder

Approved in Canada as Cipralex for:

• Major depressive disorder
• Generalized anxiety disorder
• Social anxiety disorder

Who Is Running the Clinical Trial?

University of Cincinnati

Lead Sponsor

Trials

442

Recruited

639,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

Escitalopram, a more active isomer of citalopram, showed a faster onset of action and greater overall effectiveness in treating major depressive disorder compared to citalopram, with significant improvements in depression and anxiety symptoms observed as early as one week into treatment.

Both escitalopram and citalopram were effective in reducing symptoms of depression and anxiety compared to placebo, but escitalopram demonstrated statistically significant advantages over citalopram at multiple time points during the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials. Gorman, JM., Korotzer, A., Su, G.[2019]

Escitalopram oxalate is an effective antidepressant that has shown robust efficacy in treating major depressive disorder and anxiety disorders, with significant improvements observed compared to placebo in multiple clinical trials.

The medication has a favorable safety profile, with a low rate of discontinuation due to adverse events, and the most common side effects, such as nausea and insomnia, were generally mild, affecting less than 10% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escitalopram. Burke, WJ.[2022]

Escitalopram is effective and well tolerated for both short- and long-term treatment of generalized anxiety disorder, based on evidence from randomized placebo-controlled and comparator-controlled trials.

Compared to benzodiazepines and the SSRI paroxetine, escitalopram offers advantages in treating generalized anxiety disorder, making it a preferred option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escitalopram in the treatment of generalized anxiety disorder. Baldwin, DS., Nair, RV.[2013]

Escitalopram, the active s-enantiomer of citalopram, is an effective selective serotonin reuptake inhibitor (SSRI) used to treat major depressive disorder.

As an SSRI, escitalopram works by increasing serotonin levels in the brain, which can help improve mood and alleviate symptoms of depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escitalopram (Lexapro) for depression. Masilamani, S., Ruppelt, SC.[2022]

Selective serotonin reuptake inhibitors (SSRIs), particularly escitalopram, are effective in treating anxiety symptoms associated with depression, showing significant improvement compared to placebo as early as the first week of treatment.

Escitalopram not only demonstrates rapid efficacy but also has a favorable tolerability profile, making it a preferred choice over traditional anxiolytics like benzodiazepines, which have more adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of escitalopram on anxiety symptoms in depression]. Spadone, C.[2022]

Escitalopram is an effective and well-tolerated treatment for various anxiety disorders and OCD, showing at least equal efficacy to paroxetine and a quicker response in panic disorder.

It has a favorable safety profile with fewer discontinuation symptoms compared to paroxetine, and its pharmacokinetics allow for convenient once-daily dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escitalopram: a review of its use in the management of anxiety disorders. Dhillon, S., Scott, LJ., Plosker, GL.[2019]

In a prospective open-label trial involving 10 patients with generalized social anxiety disorder, citalopram was found to be well tolerated and led to significant improvements in all outcome measures.

The study suggests that citalopram may be a safe and effective treatment option for patients who have not responded to or tolerated previous treatments for social anxiety disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citalopram for social anxiety disorder: an open-label pilot study in refractory and nonrefractory patients. Simon, NM., Korbly, NB., Worthington, JJ., et al.[2019]

In a study of nine patients with generalized social anxiety disorder, citalopram was found to be generally well-tolerated and led to significant improvements in all measured outcomes.

Seven out of nine patients achieved responder status, indicating that citalopram may be a safe and effective treatment option for social anxiety disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citalopram for social phobia: a clinical case series. Simon, NM., Sharma, SG., Worthington, JJ., et al.[2019]

In a study of 366 outpatients with panic disorder, escitalopram significantly reduced the frequency of panic attacks compared to placebo, demonstrating its efficacy in treating this condition.

Escitalopram was found to be safe and well tolerated, with a low rate of discontinuation due to adverse events, similar to that of the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. Stahl, SM., Gergel, I., Li, D.[2022]

A study evaluated the adherence to prescribing guidelines for citalopram and found that implementing an EMIS safety prompt and providing prescriber training led to a significant reduction in incorrect prescriptions for patients over 65, from 8 to 1.

The interventions also decreased dangerous drug interactions involving citalopram from 44 to 8 and overall unsafe prescribing from 47 to 9, highlighting improved patient safety and resource use that could be applied to other medications with safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safer citalopram use in primary care: Can staff education and prescribing prompts improve adherence to national guidance? A closed loop clinical audit, service evaluation and quality improvement study. Waller, M.[2023]

Escitalopram is an effective first-line treatment for anxiety disorders such as panic disorder, generalized anxiety disorder (GAD), social anxiety disorder, and obsessive-compulsive disorder (OCD), showing significant efficacy compared to placebo in multiple studies involving various patient populations.

The drug is well-tolerated, with low withdrawal rates due to adverse events (7% for escitalopram vs. 8% for placebo), and it demonstrates a reduced risk of relapse in long-term studies, making it a reliable option for ongoing management of these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and tolerability of escitalopram in anxiety disorders: a review]. Pelissolo, A.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0924977X16000675

Efficacy of escitalopram in the treatment of social anxiety ... In this meta-analysis, all doses of escitalopram showed significant superiority in efficacy versus placebo in the treatment of patients with SAD. Previous ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10675869/

Escitalopram versus other antidepressive agents for major ... Escitalopram was shown to be significantly more effective than citalopram in achieving acute response (RR 0.67, 95% CI 0.50—0.87).

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557734/

Escitalopram - StatPearls - NCBI Bookshelf Escitalopram is also used off-label for conditions such as social anxiety disorder, obsessive-compulsive disorder, panic disorder, posttraumatic ...

4. nature.com nature.com/articles/s41598-025-18517-6

Effectiveness and safety of escitalopram treatment ... The placebo effect resulted in a 43% reduction in symptom severity, while the fixed dose of 10 mg/day, the fixed dose of 20 mg/day and the ...

5. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2798510

Mindfulness-Based Stress Reduction vs Escitalopram for ... This randomized clinical trial evaluates whether mindfulness-based stress reduction is noninferior to escitalopram in the treatment of anxiety disorders.

6. fda.gov fda.gov/media/135185/download

Lexapro (escitalopram oxalate) the safety findings were consistent with the known safety and tolerability profile for Lexapro. Safety and effectiveness of Lexapro has not been established ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/escitalopram-oral-route/description/drg-20063707

Escitalopram (oral route) - Side effects & dosage Escitalopram is used to treat depression and generalized anxiety disorder (GAD). ... Safety and efficacy have not been established.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5014051/

Citalopram and escitalopram: adverse cardiac outcomes in ... The new FDA recommendations state that citalopram should not be used at doses greater than 40 mg per day in healthy adults, and not exceed 20 mg per day in the ...

9. fda.gov fda.gov/media/169201/download

CDER Lexapro Safety and Drug Utilization Review and/or Orthostatic intolerance” while taking escitalopram for anxiety. She “was also diagnosed with Chronic Fatigue Syndrome.” The symptoms ...